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| | ==Crystal Structure of Arabidopsis thaliana 5'-Methylthioadenosine nucleosidase in complex with Formycin A== | | ==Crystal Structure of Arabidopsis thaliana 5'-Methylthioadenosine nucleosidase in complex with Formycin A== |
| - | <StructureSection load='2qtt' size='340' side='right' caption='[[2qtt]], [[Resolution|resolution]] 1.93Å' scene=''> | + | <StructureSection load='2qtt' size='340' side='right'caption='[[2qtt]], [[Resolution|resolution]] 1.93Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2qtt]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QTT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2QTT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2qtt]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QTT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2QTT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADE:ADENINE'>ADE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMC:(1S)-1-(7-AMINO-1H-PYRAZOLO[4,3-D]PYRIMIDIN-3-YL)-1,4-ANHYDRO-D-RIBITOL'>FMC</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADE:ADENINE'>ADE</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FMC:(1S)-1-(7-AMINO-1H-PYRAZOLO[4,3-D]PYRIMIDIN-3-YL)-1,4-ANHYDRO-D-RIBITOL'>FMC</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qtg|2qtg]], [[2qsu|2qsu]], [[1nc3|1nc3]], [[2h8g|2h8g]], [[1nc1|1nc1]], [[2qt9|2qt9]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2qtg|2qtg]], [[2qsu|2qsu]], [[1nc3|1nc3]], [[2h8g|2h8g]], [[1nc1|1nc1]], [[2qt9|2qt9]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AT4g38800 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 ARATH])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AT4g38800 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 ARATH])</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Methylthioadenosine_nucleosidase Methylthioadenosine nucleosidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.16 3.2.2.16] </span></td></tr> | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Methylthioadenosine_nucleosidase Methylthioadenosine nucleosidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.2.16 3.2.2.16] </span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2qtt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qtt OCA], [http://pdbe.org/2qtt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2qtt RCSB], [http://www.ebi.ac.uk/pdbsum/2qtt PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2qtt ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2qtt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2qtt OCA], [https://pdbe.org/2qtt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2qtt RCSB], [https://www.ebi.ac.uk/pdbsum/2qtt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2qtt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MTN1_ARATH MTN1_ARATH]] Enzyme of the methionine cycle that catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (MTA) to adenine and 5'-methylthioribose. Contributes to the maintenance of AdoMet homeostasis and is required to sustain high rates of ethylene synthesis. Inactive towards S-adenosylhomocysteine (SAH/AdoHcy).<ref>PMID:17144895</ref> <ref>PMID:18342331</ref> <ref>PMID:20345605</ref> | + | [[https://www.uniprot.org/uniprot/MTN1_ARATH MTN1_ARATH]] Enzyme of the methionine cycle that catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (MTA) to adenine and 5'-methylthioribose. Contributes to the maintenance of AdoMet homeostasis and is required to sustain high rates of ethylene synthesis. Inactive towards S-adenosylhomocysteine (SAH/AdoHcy).<ref>PMID:17144895</ref> <ref>PMID:18342331</ref> <ref>PMID:20345605</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Arath]] | | [[Category: Arath]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Methylthioadenosine nucleosidase]] | | [[Category: Methylthioadenosine nucleosidase]] |
| | [[Category: Howell, P L]] | | [[Category: Howell, P L]] |
| Structural highlights
Function
[MTN1_ARATH] Enzyme of the methionine cycle that catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (MTA) to adenine and 5'-methylthioribose. Contributes to the maintenance of AdoMet homeostasis and is required to sustain high rates of ethylene synthesis. Inactive towards S-adenosylhomocysteine (SAH/AdoHcy).[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
5'-Methylthioadenosine (MTA)/S-adenosylhomocysteine (SAH) nucleosidase (MTAN) is essential for cellular metabolism and development in many bacterial species. While the enzyme is found in plants, plant MTANs appear to select for MTA preferentially, with little or no affinity for SAH. To understand what determines substrate specificity in this enzyme, MTAN homologues from Arabidopsis thaliana (AtMTAN1 and AtMTAN2, which are referred to as AtMTN1 and AtMTN2 in the plant literature) have been characterized kinetically. While both homologues hydrolyze MTA with comparable kinetic parameters, only AtMTAN2 shows activity towards SAH. AtMTAN2 also has higher catalytic activity towards other substrate analogues with longer 5'-substituents. The structures of apo AtMTAN1 and its complexes with the substrate- and transition-state-analogues, 5'-methylthiotubercidin and formycin A, respectively, have been determined at 2.0-1.8 A resolution. A homology model of AtMTAN2 was generated using the AtMTAN1 structures. Comparison of the AtMTAN1 and AtMTAN2 structures reveals that only three residues in the active site differ between the two enzymes. Our analysis suggests that two of these residues, Leu181/Met168 and Phe148/Leu135 in AtMTAN1/AtMTAN2, likely account for the divergence in specificity of the enzymes. Comparison of the AtMTAN1 and available Escherichia coli MTAN (EcMTAN) structures suggests that a combination of differences in the 5'-alkylthio binding region and reduced conformational flexibility in the AtMTAN1 active site likely contribute to its reduced efficiency in binding substrate analogues with longer 5'-substituents. In addition, in contrast to EcMTAN, the active site of AtMTAN1 remains solvated in its ligand-bound forms. As the apparent pK(a) of an amino acid depends on its local environment, the putative catalytic acid Asp225 in AtMTAN1 may not be protonated at physiological pH and this suggests the transition state of AtMTAN1, like human MTA phosphorylase and Streptococcus pneumoniae MTAN, may be different from that found in EcMTAN.
Molecular determinants of substrate specificity in plant 5'-methylthioadenosine nucleosidases.,Siu KK, Lee JE, Sufrin JR, Moffatt BA, McMillan M, Cornell KA, Isom C, Howell PL J Mol Biol. 2008 Apr 18;378(1):112-28. Epub 2008 Feb 8. PMID:18342331[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Burstenbinder K, Rzewuski G, Wirtz M, Hell R, Sauter M. The role of methionine recycling for ethylene synthesis in Arabidopsis. Plant J. 2007 Jan;49(2):238-49. Epub 2006 Nov 27. PMID:17144895 doi:http://dx.doi.org/10.1111/j.1365-313X.2006.02942.x
- ↑ Siu KK, Lee JE, Sufrin JR, Moffatt BA, McMillan M, Cornell KA, Isom C, Howell PL. Molecular determinants of substrate specificity in plant 5'-methylthioadenosine nucleosidases. J Mol Biol. 2008 Apr 18;378(1):112-28. Epub 2008 Feb 8. PMID:18342331 doi:10.1016/j.jmb.2008.01.088
- ↑ Burstenbinder K, Waduwara I, Schoor S, Moffatt BA, Wirtz M, Minocha SC, Oppermann Y, Bouchereau A, Hell R, Sauter M. Inhibition of 5'-methylthioadenosine metabolism in the Yang cycle alters polyamine levels, and impairs seedling growth and reproduction in Arabidopsis. Plant J. 2010 Jun 1;62(6):977-88. doi: 10.1111/j.1365-313X.2010.04211.x. Epub, 2010 Mar 19. PMID:20345605 doi:http://dx.doi.org/10.1111/j.1365-313X.2010.04211.x
- ↑ Siu KK, Lee JE, Sufrin JR, Moffatt BA, McMillan M, Cornell KA, Isom C, Howell PL. Molecular determinants of substrate specificity in plant 5'-methylthioadenosine nucleosidases. J Mol Biol. 2008 Apr 18;378(1):112-28. Epub 2008 Feb 8. PMID:18342331 doi:10.1016/j.jmb.2008.01.088
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